Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony- forming units-granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha
Injection of human rIL-1 alpha in intact normal mice has positive and negative effects on myelopoiesis. Within 6 h postinjection, peripheral neutrophilia can be demonstrated. However, bone marrow and spleen cells capable of inhibiting CFU-granulocyte macrophage proliferation are detected between 6 a...
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Veröffentlicht in: | The Journal of immunology (1950) 1989-12, Vol.143 (12), p.4171-4179 |
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Zusammenfassung: | Injection of human rIL-1 alpha in intact normal mice has positive and negative effects on myelopoiesis. Within 6 h postinjection, peripheral neutrophilia can be demonstrated. However, bone marrow and spleen cells capable of inhibiting CFU-granulocyte macrophage proliferation are detected between 6 and 48 h postinjection. These myelopoietic suppressor cells belong to the monocytic lineage and are identical to inhibitory cells induced by PGE2. Treatment of mice with indomethacin, a PG synthesis inhibitor, completely blocked the generation of IL-1-alpha-induced myelopoietic suppressor cells, and significantly enhanced femoral and splenic CFU-GM proliferation after a single injection of 0.4 microgram/mouse IL-1. The peripheral blood neutrophilia observed within 6 h after IL-1 injection was delayed to 18 to 24 h postinjection in indomethacin-pretreated mice. In mice treated with four consecutive daily injections of 0.4 microgram IL-1, a sustained peripheral neutrophilia was observed. IL-1 had little effect on femoral CFU-GM in these animals, however, splenic CFU-GM was increased 7- to 10-fold by 4 to 7 days postinjection. In IL-1 plus indomethacin-treated mice, sustained peripheral neutrophilia was observed although to a lesser degree than with IL-1 alone. Marrow CFU-GM were relatively unaffected, however, splenic CFU-GM were increased by 27-fold. These results indicate that the in vivo administration of IL-1 results in neutrophilia and generation of myelopoietic suppressive effects, mediated by cyclo-oxygenase pathway products. Blockade of PG synthesis by using the cyclo-oxygenase inhibitor indomethacin abrogates the myelopoietic suppressive effects associated with IL-1 administration and optimizes its myelopoietic stimulatory capacity. The inclusion of a cyclo-oxygenase inhibitor may have significant relevance to the clinical use of IL-1. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.143.12.4171 |